The Voltage-Dependent Anion Channel: Characterization, Modulation, and Role in Mitochondrial Function in Cell Life and Death

2003 ◽  
Vol 39 (3) ◽  
pp. 279-292 ◽  
Author(s):  
Varda Shoshan-Barmatz ◽  
Dan Gincel
Keyword(s):  
Mitochondrial Function ◽  
Anion Channel ◽  
Voltage Dependent Anion Channel ◽  
Life And Death ◽  
Channel Characterization ◽  
Cell Life ◽  
Voltage Dependent

scholarly journals PDE5 inhibition rescues mitochondrial dysfunction and angiogenic responses induced by Akt3 inhibition by promotion of PRC expression

2020 ◽  
Vol 295 (52) ◽  
pp. 18091-18104
Author(s):  
Daniel G. Corum ◽  
Dorea P. Jenkins ◽  
James A. Heslop ◽  
Lacey M. Tallent ◽  
Gyda C. Beeson ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Oxygen Consumption ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Anion Channel ◽  
Specific Protein ◽  
Direct Link ◽  
Voltage Dependent Anion Channel ◽  
Mitochondrial Homeostasis ◽  
Voltage Dependent

Akt3 regulates mitochondrial content in endothelial cells through the inhibition of PGC-1α nuclear localization and is also required for angiogenesis. However, whether there is a direct link between mitochondrial function and angiogenesis is unknown. Here we show that Akt3 depletion in primary endothelial cells results in decreased uncoupled oxygen consumption, increased fission, decreased membrane potential, and increased expression of the mitochondria-specific protein chaperones, HSP60 and HSP10, suggesting that Akt3 is required for mitochondrial homeostasis. Direct inhibition of mitochondrial homeostasis by the model oxidant paraquat results in decreased angiogenesis, showing a direct link between angiogenesis and mitochondrial function. Next, in exploring functional links to PGC-1α, the master regulator of mitochondrial biogenesis, we searched for compounds that induce this process. We found that, sildenafil, a phosphodiesterase 5 inhibitor, induced mitochondrial biogenesis as measured by increased uncoupled oxygen consumption, mitochondrial DNA content, and voltage-dependent anion channel protein expression. Sildenafil rescued the effects on mitochondria by Akt3 depletion or pharmacological inhibition and promoted angiogenesis, further supporting that mitochondrial homeostasis is required for angiogenesis. Sildenafil also induces the expression of PGC-1 family member PRC and can compensate for PGC-1α activity during mitochondrial stress by an Akt3-independent mechanism. The induction of PRC by sildenafil depends upon cAMP and the transcription factor CREB. Thus, PRC can functionally substitute during Akt3 depletion for absent PGC-1α activity to restore mitochondrial homeostasis and promote angiogenesis. These findings show that mitochondrial homeostasis as controlled by the PGC family of transcriptional activators is required for angiogenic responses.

scholarly journals Alpha-Synuclein and Mitochondrial Dysfunction in Parkinson’s Disease: The Emerging Role of VDAC

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 718
Author(s):  
Pierpaolo Risiglione ◽  
Federica Zinghirino ◽  
Maria Carmela Di Rosa ◽  
Andrea Magrì ◽  
Angela Messina
Keyword(s):  
Parkinson’S Disease ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Anion Channel ◽  
Alpha Synuclein ◽  
Voltage Dependent Anion Channel ◽  
Cytosolic Proteins ◽  
Pathological Conditions ◽  
Voltage Dependent

Alpha-Synuclein (αSyn) is a protein whose function is still debated, as well as its role in modulation of mitochondrial function in both physiological and pathological conditions. Mitochondrial porins or Voltage-Dependent Anion Channel (VDAC) proteins are the main gates for ADP/ATP and various substrates towards the organelle. Furthermore, they act as a mitochondrial hub for many cytosolic proteins, including αSyn. This review analyzes the main aspects of αSyn-mitochondria interaction, focusing on the role of VDAC and its emerging involvement in the pathological processes.

scholarly journals VDAC1 in the diseased myocardium and the effect of VDAC1-interacting compound on atrial fibrosis induced by hyperaldosteronism

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hadar Klapper-Goldstein ◽  
Ankit Verma ◽  
Sigal Elyagon ◽  
Roni Gillis ◽  
Michael Murninkas ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Apoptotic Cell ◽  
Anion Channel ◽  
Immunohistochemical Analysis ◽  
Voltage Dependent Anion Channel ◽  
Cardiac Tissues ◽  
Therapeutic Implications ◽  
Voltage Dependent ◽  
Models Of Lupus

AbstractThe voltage-dependent anion channel 1 (VDAC1) is a key player in mitochondrial function. VDAC1 serves as a gatekeeper mediating the fluxes of ions, nucleotides, and other metabolites across the outer mitochondrial membrane, as well as the release of apoptogenic proteins initiating apoptotic cell death. VBIT-4, a VDAC1 oligomerization inhibitor, was recently shown to prevent mitochondrial dysfunction and apoptosis, as validated in mouse models of lupus and type-2 diabetes. In the present study, we explored the expression of VDAC1 in the diseased myocardium of humans and rats. In addition, we evaluated the effect of VBIT-4 treatment on the atrial structural and electrical remodeling of rats exposed to excessive aldosterone levels. Immunohistochemical analysis of commercially available human cardiac tissues revealed marked overexpression of VDAC1 in post-myocardial infarction patients, as well as in patients with chronic ventricular dilatation\dysfunction. In agreement, rats exposed to myocardial infarction or to excessive aldosterone had a marked increase of VDAC1 in both ventricular and atrial tissues. Immunofluorescence staining indicated a punctuated appearance typical for mitochondrial-localized VDAC1. Finally, VBIT-4 treatment attenuated the atrial fibrotic load of rats exposed to excessive aldosterone without a notable effect on the susceptibility to atrial fibrillation episodes induced by burst pacing. Our results indicate that VDAC1 overexpression is associated with myocardial abnormalities in common pathological settings. Our data also indicate that inhibition of the VDAC1 can reduce excessive fibrosis in the atrial myocardium, a finding which may have important therapeutic implications. The exact mechanism\s of this beneficial effect need further studies.

scholarly journals Identification of two voltage-dependent anion channel-like protein sequences conserved in Kinetoplastida

2012 ◽  
Vol 8 (3) ◽  
pp. 446-449 ◽  
Author(s):  
Nadine Flinner ◽  
Enrico Schleiff ◽  
Oliver Mirus
Keyword(s):  
Outer Membrane ◽  
Trypanosoma Brucei ◽  
Protein Sequences ◽  
Anion Channel ◽  
Mitochondrial Outer Membrane ◽  
Voltage Dependent Anion Channel ◽  
Voltage Dependent

The eukaryotic porin superfamily consists of two families, voltage-dependent anion channel (VDAC) and Tom40, which are both located in the mitochondrial outer membrane. In Trypanosoma brucei , only a single member of the VDAC family has been described. We report the detection of two additional eukaryotic porin-like sequences in T. brucei . By bioinformatic means, we classify both as putative VDAC isoforms.

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